Abstract
Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3260-3264 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 78 |
| Issue number | 5 I |
| DOIs | |
| State | Published - 1981 |
Fingerprint
ASJC Scopus subject areas
- Genetics
- General
Cite this
Adenosine receptors and behavioral actions of methylxanthines [caffeine/theophylline/N 6-cyclohexyladenosine/N 6-(phenylisopropyl)adenosine]. / Snyder, Solomon H; Katims, J. J.; Annau, Z.; Bruns, R. F.; Daly, J. W.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 78, No. 5 I, 1981, p. 3260-3264.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adenosine receptors and behavioral actions of methylxanthines [caffeine/theophylline/N 6-cyclohexyladenosine/N 6-(phenylisopropyl)adenosine]
AU - Snyder, Solomon H
AU - Katims, J. J.
AU - Annau, Z.
AU - Bruns, R. F.
AU - Daly, J. W.
PY - 1981
Y1 - 1981
N2 - Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.
AB - Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.
UR - http://www.scopus.com/inward/record.url?scp=0001441518&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0001441518&partnerID=8YFLogxK
U2 - 10.1073/pnas.78.5.3260
DO - 10.1073/pnas.78.5.3260
M3 - Article
C2 - 6265942
AN - SCOPUS:0001441518
VL - 78
SP - 3260
EP - 3264
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5 I
ER -